Orientation To Pharmacology


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Orientation To Pharmacology

  1. 1. Medication Administration BY Thomas Petricini
  2. 2. Orientation to Pharmacology FOUR BASIC TERMS <ul><li>DRUG </li></ul><ul><li>A drug is defined as any chemical that </li></ul><ul><li>can affect living processes. </li></ul><ul><li>Virtually all chemicals can be considered drugs, since, when exposure is sufficiently high, all chemicals will have some effect on life. </li></ul>.
  3. 3. FOUR BASIC TERMS <ul><li>Pharmacology. </li></ul><ul><li>T he study of drugs and their </li></ul><ul><li>interactions with living systems. </li></ul><ul><li>Encompasses the study of the physical and chemical properties of drugs as well as their biochemical and physiologic effects </li></ul>
  4. 4. FOUR BASIC TERMS <ul><li>Pharmacology </li></ul><ul><li>I ncludes knowledge of the history, sources, and uses of drugs </li></ul><ul><li>knowledge of drug </li></ul><ul><li>absorption, distribution, metabolism, and excretion </li></ul>
  5. 5. FOUR BASIC TERMS <ul><li>Clinical Pharmacology </li></ul><ul><li>D efined as the study of drugs in humans </li></ul><ul><li>Includes the study of drugs in patients as well as in healthy volunteers (during new drug development). </li></ul>
  6. 6. FOUR BASIC TERMS <ul><li>Therapeutics. </li></ul><ul><li>T he use of drugs to diagnose, prevent, or treat disease or to prevent pregnancy. </li></ul><ul><li>The medical use of drugs. </li></ul>
  7. 7. PROPERTIES OF AN IDEAL DRUG <ul><li>Effectiveness. </li></ul><ul><li>Effective drug is one that elicits the responses for which it is given </li></ul><ul><li>Effectiveness is the most important property </li></ul><ul><li>a drug can have. </li></ul>
  8. 8. PROPERTIES OF AN IDEAL DRUG <ul><li>Safety . </li></ul><ul><li>A safe drug is defined as one that cannot produce harmful effects even if administered in very high doses and for a very long time </li></ul><ul><li>The chances of producing adverse effects can be reduced by proper drug selection and proper dosing. </li></ul>
  9. 9. PROPERTIES OF AN IDEAL DRUG <ul><li>Selectivity. </li></ul><ul><li>A selective drug is defined as one that elicits only the response for which it is given . </li></ul><ul><li>A selective drug would not produce side effects. </li></ul><ul><li>All medications cause side effects </li></ul>
  10. 10. PROPERTIES OF AN IDEAL DRUG <ul><li>Ease of Administration </li></ul><ul><li>An ideal drug should be simple to administer: the route should be convenient, and the number of doses per day should be low </li></ul>
  11. 11. PROPERTIES OF AN IDEAL DRUG <ul><li>Ease of administration </li></ul><ul><li>In addition to convenience, ease of administration has two other benefits: </li></ul><ul><li>it can enhance patient adherence </li></ul><ul><li>it can decrease administration errors. </li></ul>
  12. 12. PROPERTIES OF AN IDEAL DRUG <ul><li>Freedom from Drug Interactions </li></ul><ul><li>When a patient is taking two or more drugs, those drugs can interact. . </li></ul><ul><li>An ideal drug would not interact with other agents. </li></ul><ul><li>Few medicines are devoid of significant interactions. </li></ul>
  13. 13. PROPERTIES OF AN IDEAL DRUG <ul><li>Low Cost </li></ul><ul><li>An ideal drug would be easy to afford. </li></ul><ul><li>The cost of drugs can be a substantial </li></ul><ul><li>financial burden </li></ul>
  14. 14. PROPERTIES OF AN IDEAL DRUG <ul><li>Chemical Stability . </li></ul><ul><li>Some drugs lose effectiveness during storage. </li></ul><ul><li>Others, which may be stable on the shelf, can rapidly lose effectiveness when put into solution </li></ul><ul><li>These losses in efficacy result from chemical instability. </li></ul><ul><li>An ideal drug would retain its activity indefinitely, both on the shelf and in solution. </li></ul>
  15. 15. PROPERTIES OF AN IDEAL DRUG <ul><li>Possession of a Simple Generic Name . </li></ul><ul><li>Generic names of drugs are usually complex, and therefore difficult to remember and pronounce. </li></ul><ul><li>As a rule, the trade name for a drug is much simpler than its generic name. </li></ul><ul><li>An ideal drug should have a generic name that is easy to recall and pronounce. </li></ul>
  16. 16. THE THERAPEUTIC OBJECTIVE <ul><li>The objective of drug therapy is to provide maximum benefit with minimum harm </li></ul><ul><li>Nurses have a critical responsibility in achieving the therapeutic objective. </li></ul><ul><li>In order to meet this responsibility </li></ul><ul><li>you must understand drugs . </li></ul>
  17. 17. FACTORS THAT DETERMINE THE INTENSITY OF DRUG RESPONSES <ul><li>Administration </li></ul><ul><li>Dosage size and the route and timing of administration are important determinants of drug responses. </li></ul><ul><li>Unfortunately, because of poor patient adherence and medication errors drugs are not always administered as prescribed. </li></ul><ul><li>The result may be toxicity (if the dosage is too high) or treatment failure (if the dosage is too low). </li></ul>
  18. 18. FACTORS THAT DETERMINE THE INTENSITY OF DRUG RESPONSES <ul><li>Pharmacokinetics </li></ul><ul><li>Pharmacokinetic processes determine how much of an administered dose gets to its sites of action. There are four major pharmacokinetic processes: Drug absorption, </li></ul><ul><li>Drug distribution, </li></ul><ul><li>Drug metabolism </li></ul><ul><li>Drug excretion. </li></ul><ul><li>These processes can be thought of as the impact of the body on drugs </li></ul>
  19. 19. FACTORS THAT DETERMINE THE INTENSITY OF DRUG RESPONSES <ul><li>Pharmacodynamics </li></ul><ul><li>P harmacodynamic processes determine the nature and intensity of the response. </li></ul><ul><li>Pharmacodynamics can be thought of as the impact of drugs on the body. </li></ul><ul><li>In most cases, the initial step leading to a response is the binding of a drug to its receptor. </li></ul>
  20. 20. FACTORS THAT DETERMINE THE INTENSITY OF DRUG RESPONSES <ul><li>Sources of Individual Variation </li></ul><ul><li>S ources of individual variation include: </li></ul><ul><li>Drug interactions </li></ul><ul><li>Physiologic variables (age, gender, weight); </li></ul><ul><li>Pathologic variables (especially diminished function </li></ul><ul><li>of the kidneys and liver) </li></ul><ul><li>Genetic variables. </li></ul><ul><li>Because individuals differ from one another, no two patients will respond identically to the same drug regimen. </li></ul>
  21. 21. Pharmacology and the Nursing Process <ul><li>Why Study Pharmacology ? </li></ul><ul><li>You must acquire a broad base of pharmacologic knowledge so as to contribute fully to achieving the therapeutic objective. </li></ul><ul><li>To provide professional care, you must understand drugs; the stronger your knowledge of pharmacology, the more you will be able to anticipate drug responses and not simply react to them after the fact. </li></ul><ul><li>You are the patient's last line of defense against medication errors </li></ul>
  22. 22. APPLICATION OF PHARMACOLOGY IN PATIENT CARE <ul><li>Preadministration Assessment </li></ul><ul><li>All drug therapy begins with assessment of the patient. </li></ul><ul><li>Assessment has three basic goals: </li></ul><ul><li>Collecting baseline data needed to evaluate </li></ul><ul><li>therapeutic and adverse responses, </li></ul><ul><li>Identifying high-risk patients, </li></ul><ul><li>Assessing the patient's capacity for self-care. </li></ul>
  23. 23. Collecting Baseline Data <ul><li>Baseline data are needed to evaluate drug responses, both therapeutic and adverse </li></ul><ul><li>Example, </li></ul><ul><li>If we plan to give a drug to lower blood pressure, we must know the patient's blood pressure prior to treatment. Without such baseline data, we would have no way of determining the effectiveness of our drug </li></ul>
  24. 24. Identifying High-Risk Patients. <ul><li>Important Predisposing Factors </li></ul><ul><li>Pathophysiology(especially liver and kidney </li></ul><ul><li>dysfunction) </li></ul><ul><li>Genetic Factors </li></ul><ul><li>Drug Allergies ( Penicillin) </li></ul><ul><li>Pregnancy </li></ul><ul><li>Old Age </li></ul><ul><li>Extreme Youth. </li></ul>
  25. 25. Identifying patients who are at high risk of reacting adversely . <ul><li>The patient history </li></ul><ul><li>Physical examination </li></ul><ul><li>Laboratory data. </li></ul>
  26. 26. APPLICATION OF PHARMACOLOGY IN PATIENT CARE Planning / Implementation / Evaluation <ul><li>Dosage and Administration </li></ul><ul><li>Although you can implement the Five Rights without a detailed knowledge of pharmacology, having this knowledge can help reduce your contribution to medication errors. </li></ul>
  27. 27. APPLICATION OF PHARMACOLOGY IN PATIENT CARE Planning / Implementation / Evaluation <ul><li>Examples </li></ul><ul><li>Certain drugs have more than one indication, and dosage may differ depending on which indication the drug is used for. </li></ul><ul><li>Many drugs can be administered by more than one route, and dosage may differ depending upon the route selected </li></ul>
  28. 28. APPLICATION OF PHARMACOLOGY IN PATIENT CARE <ul><li>Evaluating Therapeutic Responses. </li></ul><ul><li>In order to make an evaluation, you must know the rationale for treatment and the nature and time course of the intended response. </li></ul>
  29. 29. APPLICATION OF PHARMACOLOGY IN PATIENT CARE <ul><li>Promoting Patient Adherence </li></ul><ul><li>( Compliance ) </li></ul><ul><li>If we are to achieve the therapeutic objective, adherence is essential </li></ul><ul><li>By educating patients about the drugs they are taking, you can help elicit the required participation. </li></ul>
  30. 30. APPLICATION OF PHARMACOLOGY IN PATIENT CARE <ul><li>Minimizing Adverse Effect      </li></ul><ul><li>The major adverse effects the drug can produce </li></ul><ul><li> The time when these reactions are likely to occur </li></ul><ul><li>   Early signs that an adverse reaction is developing </li></ul><ul><li>Interventions that can minimize discomfort and harm </li></ul>
  31. 31. APPLICATION OF PHARMACOLOGY IN PATIENT CARE <ul><li>Minimizing Adverse Interactions </li></ul><ul><li>When a patient is taking two or more drugs, those drugs may interact with one another to diminish therapeutic effects or intensify adverse effects </li></ul><ul><li>As a nurse, you can help reduce the incidence and intensity of adverse interactions in several ways. </li></ul>
  32. 32. APPLICATION OF PHARMACOLOGY IN PATIENT CARE <ul><li>These include: </li></ul><ul><li>Taking a thorough drug history </li></ul><ul><li>Advising the patient to avoid over the counter drugs that can interact with the prescribed medication, </li></ul><ul><li>Monitoring for adverse interactions known to occur between the drugs the patient is taking </li></ul><ul><li>Being alert for as-yet unknown interactions. </li></ul>
  33. 33. APPLICATION OF PHARMACOLOGY IN PATIENT CARE <ul><li>Teaching . </li></ul><ul><li>In your role as educator, you must give the patient the following information: </li></ul><ul><li>      Drug name and therapeutic category ( penicillin: </li></ul><ul><li>antibiotic) </li></ul><ul><li>      Dosage size </li></ul><ul><li>      Dosing schedule </li></ul><ul><li>     </li></ul>
  34. 34. APPLICATION OF PHARMACOLOGY IN PATIENT CARE <ul><li>Teaching </li></ul><ul><li>Route and technique of administration </li></ul><ul><li>Expected therapeutic response and when it should </li></ul><ul><li>develop </li></ul><ul><li>Nondrug measures to enhance therapeutic </li></ul><ul><li>responses     </li></ul><ul><li>Duration of treatment </li></ul><ul><li>     Method of drug storage </li></ul><ul><li>      </li></ul>
  35. 35. APPLICATION OF PHARMACOLOGY IN PATIENT CARE <ul><li>Teaching </li></ul><ul><li>Symptoms of major adverse effects, and measures to minimize discomfort and harm </li></ul><ul><li>      Major adverse drug-drug and drug-food interactions </li></ul><ul><li>      Whom to contact in the event of therapeutic failure, severe adverse reactions, or severe adverse interactions </li></ul>
  36. 36. APPLICATION OF PHARMACOLOGY IN PATIENT CARE <ul><li>To be a good drug educator, you must know pharmacology. </li></ul>
  37. 37. Drug Regulation <ul><li>FDA </li></ul>The origins of the Food and Drug Administration can be traced back to 1862, when President Lincoln appointed chemist Charles M. Wetherill to head the Chemical Division in the new U. S. Department of Agriculture. In the following decade Wetherill's successor as chief chemist of the USDA, Peter Collier, began working on the ubiquitous problem of food adulteration. Harvey W. Wiley replaced Collier in 1883, leading the division as it grew into the Bureau of Chemistry in 1901. The bureau was charged to enforce the first comprehensive federal statute of its kind, the Federal Food and Drugs Act, when that law was passed in 1906.
  38. 38. Drug Regulation Federal Pure Food and Drug Act of 1906. <ul><li>The first American law to regulate drugs was the Federal Pure Food and Drug Act of 1906. </li></ul><ul><li>It required only that drugs be free of adulterants. </li></ul><ul><li>The law said nothing about drug safety or effectiveness. </li></ul>
  39. 39. Drug Regulation Food, Drug and Cosmetic Act, 1938 <ul><li>First legislation to regulate drug safety </li></ul><ul><li>Tragedy in which more than 100 people died following use of a new medication </li></ul><ul><li>Congress required that all new drugs undergo testing for toxicity </li></ul><ul><li>The results of these tests were to be reviewed by the Food and Drug Administration (FDA)   </li></ul>
  40. 40. Drug Regulation Harris-Kefauver Amendments to the Food, Drug and Cosmetic Act 1962. <ul><li>This law was created in response to the thalidomide tragedy that occurred in Europe in the early 1960s </li></ul><ul><li>One of the bill's major provisions was to require proof of effectiveness before a new drug could be marketed. </li></ul><ul><li>Remarkably, this was the first law to demand that drugs actually be of some benefit. </li></ul>
  41. 41. Drug Regulation Harris-Kefauver Amendments to the Food, Drug and Cosmetic Act 1962. <ul><li>The new act also required that all drugs that had been introduced between 1932 and 1962 undergo testing for effectiveness; any drug that failed to prove useful would be withdrawn. </li></ul><ul><li>Established rigorous procedures for testing new drugs. </li></ul>
  42. 42. Drug Regulation Controlled Substances Act <ul><li>This legislation set rules for the manufacture and distribution of drugs considered to have potential for abuse of the </li></ul><ul><li>Law defines categories into which controlled substances are placed . </li></ul><ul><li>The abuse potential of these agents becomes progressively less as we proceed from Schedule II to Schedule V </li></ul>
  43. 43. Drug Regulation The Orphan Drug Act (ODA) of January 1983 <ul><li>Meant to encourage pharmaceutical companies to develop drugs for diseases that have a small market </li></ul><ul><li>Companies that develop such a drug (a drug for a disorder affecting fewer than 200,000 people in the United States) may sell it without competition for seven years, [2] </li></ul>
  44. 44. Drug Regulation The Orphan Drug Act (ODA) of January 1983 <ul><li>Some statistical burdens are lessened in an effort to maintain development momentum. For example, orphan drug regulations generally acknowledge the fact that it may not be possible to test 1,000 patients in a phase III clinical trial, as fewer than that number may be afflicted with the disease in question. </li></ul>
  45. 45. Drug Names Chemical Name <ul><li>The chemical name constitutes a description of a drug using the nomenclature of chemistry </li></ul><ul><li>A drug's chemical name can be long and complex. </li></ul><ul><li>Because of their complexity, chemical names are inappropriate for everyday use </li></ul>
  46. 46. Drug Names Generic Name <ul><li>The generic name of a drug is assigned by the United States Adopted Names CounciL </li></ul><ul><li>Each drug has only one generic name. </li></ul><ul><li>The generic name is also known as the non­proprietary name or United States Adopted Name. </li></ul><ul><li>Generic names are less complex than chemical names but typically more complex than trade names. </li></ul><ul><li>Generic names are preferable to trade names for general use. </li></ul>
  47. 47. Drug Names Trade Name <ul><li>Trade names, also known as proprietary or brand names, are the names under which a drug is marketed. </li></ul><ul><li>These names are created by drug companies with the intention that they be easy for nurses, physicians, pharmacists, and consumers to recall and pronounce. </li></ul><ul><li>Since any drug can be marketed in different formulations and by multiple companies, the number of trade names that a drug can have is large. </li></ul>
  48. 48. Drug Names Trade Name <ul><li>Trade names must be approved by the FDA. </li></ul><ul><li>The review process tries to ensure that no two trade names are too similar. </li></ul><ul><li>Trade names cannot imply unlikely efficacy </li></ul>
  49. 49. Drug Classifications <ul><li>Pharmacologic- Actions –Mechanism of Action </li></ul><ul><li>Therapeutic--- What they are used for </li></ul>
  50. 50. Sources of Drug Information <ul><li>People </li></ul><ul><li>Pharmacists </li></ul><ul><li>Pharmaceutical Sales Representatives </li></ul><ul><li>Poison Control Centers </li></ul>
  51. 51. Sources of Drug Information <ul><li>Published Information </li></ul><ul><li>Text-like Books </li></ul><ul><li>Newsletters </li></ul><ul><li>Reference Books </li></ul><ul><li>PDR </li></ul><ul><li>Nurse’s Drug Handbook </li></ul>
  52. 52. Sources of Drug Information <ul><li>The Internet </li></ul><ul><li>Use Discretion </li></ul>
  53. 53. Pharmacokinetics <ul><li>Definition : </li></ul><ul><li>The term pharmacokinetics is derived from </li></ul><ul><li>two Greek words: pharnakon (drug or poison) and kinesis (motion). As this derivation implies, pharmacokinetics is the study of drug movement throughout the body </li></ul>
  54. 54. Pharmacokinetics <ul><li>Four Basic Pharmacokinetic processes: </li></ul><ul><li>Absorption </li></ul><ul><li>Distribution </li></ul><ul><li>Metabolism </li></ul><ul><li>Excretion </li></ul><ul><li>The four processes determine the Concentration of drug at its site of action </li></ul>
  55. 55. Pharmacokinetics <ul><li>Application </li></ul>
  56. 56. Absorption <ul><li>Absorption is the movement of a drug from its site of administration into the blood. </li></ul><ul><li>The rate of absorption determines how soon effects will begin. </li></ul><ul><li>The amount of absorption helps determine how intense effects will be. </li></ul>
  57. 57. Absorption <ul><li>Factors Affecting Drug Absorption </li></ul><ul><li>Rate of Dissolution </li></ul><ul><li>Surface Area </li></ul><ul><li>Blood Flow </li></ul><ul><li>Lipid Solubility </li></ul><ul><li>PH Partitioning </li></ul>
  58. 58. Absorption <ul><li>The routes of administration that are used most commonly fall into two major groups: </li></ul><ul><li>Enteral (via the gastrointestinal tract) </li></ul><ul><li>Parenteral. The literal definition of parenteral is outside the GI tract. </li></ul><ul><li>The term parenteral is used to mean by injection. The principal parenteral routes are intravenous, subcutaneous, and intramuscular: </li></ul>
  59. 59. Absorption Characteristics of Commonly Used Routes of Administration <ul><li>Intravenous </li></ul><ul><li>Barriers to Absorption. </li></ul><ul><li>When a drug is administered IV, there are no barriers to absorption </li></ul><ul><li>Absorption Pattern </li></ul><ul><li>Intravenous administration results in &quot;absorption&quot; that is both instantaneous and complete </li></ul>
  60. 60. <ul><li>IV Route Advantages. </li></ul><ul><li>Rapid Onset </li></ul><ul><li>Control. </li></ul><ul><li>Use of Large Fluid Volumes . </li></ul><ul><li>Use of Irritant Drugs </li></ul>
  61. 61. <ul><li>IV Route Disadvantages . </li></ul><ul><li>High Cost, Difficulty, and </li></ul><ul><li>Inconvenience. </li></ul><ul><li>Irreversibility </li></ul><ul><li>IV administration can be dangerous. Once a drug has been injected, there is no turning back; </li></ul>
  62. 62. <ul><li>Fluid Overload. When drugs are administered in a large volume, fluid overload can occur. This can be a significant problem for patients with hypertension, kidney disease, or heart failure. </li></ul><ul><li>Infection. Infection can occur from injecting a contaminated drug. </li></ul><ul><li>Embolism </li></ul>
  63. 63. The Importance of Reading Labels <ul><li>It must be noted that a solution prepared for use by one route will differ in concentration from a solution prepared for use by other routes. </li></ul><ul><li>Solutions intended for subcutaneous administration are concentrated, solutions intended for intravenous use are dilute. If a solution prepared for subQ use were to be inadvertently administered IV, the result could prove fatal. </li></ul>
  64. 64. <ul><li>Intramuscular </li></ul><ul><li>Barriers to Absorption </li></ul><ul><li>C apillary wall </li></ul>
  65. 65. <ul><li>Absorption Pattern. Drugs administered IM may be absorbed rapidly or slowly. </li></ul><ul><li>The rate of absorption is determined largely by two factors: </li></ul><ul><li>(1) water solubility of the drug </li></ul><ul><li>(2) blood flow to the site of injection. </li></ul>
  66. 66. <ul><li>Advantages. </li></ul><ul><li>The 1M route can be used for parenteral administration of poorly soluble drugs. tissue </li></ul><ul><li>A second advantage of the 1M route is that we can administer depot preparations (preparations from which drug is absorbed slowly over an extended time). </li></ul>
  67. 67. <ul><li>Disadvantages. </li></ul><ul><li>The major drawbacks of IM administration are discomfort and inconvenience. </li></ul><ul><li>Intramuscular injection of some preparations can be painful. </li></ul><ul><li>1M injection can cause local tissue injury and possibly nerve damage (if njection is done improperly). Like all other forms of parenteral administration, IM injections are less convenient than oral administration. </li></ul>
  68. 68. <ul><li>Subcutaneous </li></ul><ul><li>The pharmacokinetics of subQ administration are nearly identical to those of 1M administration. As with 1M administration, there are no significant barriers to absorption: </li></ul><ul><li>Because of the similarities between subQ and 1M administration, these routes have similar advantages (suitability for poorly soluble drugs and depot preparations) and similar drawbacks (discomfort, inconvenience, potential for injury </li></ul>
  69. 69. <ul><li>Oral </li></ul><ul><li>The abbreviation PO is used in reference to oral administration. This abbreviation stands for per as, a Latin phrase meaning by way of the mouth. </li></ul><ul><li>Barriers to Absorption. </li></ul><ul><li>Following oral administration, drugs may be absorbed from the stomach or intestine. : </li></ul><ul><li>the layer of epithelial cells that lines the GI tract, </li></ul><ul><li>capillary wall. </li></ul>
  70. 70. <ul><li>Because the walls of the capillaries that serve the GI tract offer no significant resistance to absorption, the major barrier to absorption is the GI epithelium. To cross this layer of tightly packed cells, drugs must pass through cells rather than between them. </li></ul>
  71. 71. <ul><li>Absorption Pattern. </li></ul><ul><li>Factors that can influence absorption include </li></ul><ul><li>1) solubility and stability of the drug </li></ul><ul><li>(2) gastric and intestinal pH </li></ul><ul><li>(3) gastric emptying time </li></ul><ul><li>(4) food in the gut </li></ul><ul><li>(5) coadministration of other drugs </li></ul><ul><li>(6) special coatings on the drug preparation. </li></ul>
  72. 72. <ul><li>Advantages. </li></ul><ul><li>Oral administration is easy, convenient, and inexpensive </li></ul><ul><li>Because of its relative ease, oral administration is the prefered route for self­medication. </li></ul>
  73. 73. <ul><li>Disadvantages. </li></ul><ul><li>Variability . The major disadvantage of PO therapy is that absorption can be highly variable. This variability makes it difficult to control the concentration of a drug at its sites of action, and </li></ul><ul><li>Inactivation. </li></ul><ul><li>Patient Requirements. </li></ul><ul><li>Local Irritation. </li></ul>
  74. 74. DISTRIBUTION <ul><li>Distribution is defined as the movement of drugs throughout the body. </li></ul><ul><li>Drug distribution is determined by three major factors: </li></ul><ul><li>Blood flow to tissues </li></ul><ul><li>The ability of a drug to exit the vascular system </li></ul><ul><li>The ability of a drug to enter cells. </li></ul>
  75. 75. Blood Flow to Tissues   <ul><li>In the first phase of distribution, drugs are carried by the blood to the tissues and organs of the body. </li></ul><ul><li>The rate at which drugs are delivered to a particular tissue is determined by blood flow to the tissue. </li></ul>
  76. 76. Exiting the Vascular System <ul><li>After a drug has been delivered to an organ or tissue via the blood, the next step is to exit the vasculature. </li></ul><ul><li>Since most drugs do not produce their effects within the blood, the ability to leave the vascular system is an important determinant of drug actions. </li></ul><ul><li>Exiting the vascular system is also necessary for drugs to undergo metabolism and excretion. Drugs in the vascular system leave the blood at capillary beds. </li></ul>
  77. 77. Entering Cells <ul><li>Some drugs must enter cells to reach their sites of action, </li></ul><ul><li>Practically all drugs must enter cells to undergo metabolism and excretion. </li></ul><ul><li>The factors that determine the ability of a drug to cross cell membranes are the same factors that determine the passage of drugs across all other membranes, namely, lipid solubility , the presence of a transport system , or both. </li></ul>
  78. 78. <ul><li>Known as biotransformation, is defined as the enzymatic alteration of drug structure. </li></ul><ul><li>Most drug metabolism takes place in the liver. </li></ul>METABOLISM
  79. 79. Drug Metabolism Therapeutic Consequences of Drug Metabolism <ul><li>Drug metabolism has six possible consequences of therapeutic significance: </li></ul><ul><li> Accelerated renal excretion of drugs </li></ul><ul><li> Drug inactivation </li></ul><ul><li>Increased therapeutic action </li></ul><ul><li>Activation of &quot;prodrugs&quot; </li></ul><ul><li>Increased toxicity </li></ul><ul><li>Decreased toxicity </li></ul><ul><li>  </li></ul>
  80. 80. Accelerated Renal Drug Excretion <ul><li>. The most important consequence of drug metabolism is promotion of renal drug excretion. </li></ul><ul><li>The kidney, which is the major organ of drug excretion, is unable to excrete drugs that are highly lipid soluble. </li></ul>
  81. 81. Drug Inactivation <ul><li>. Drug metabolism can convert pharmacologically active compounds to inactive forms. </li></ul><ul><li>This process is illustrated by the conversion of procaine (a local anesthetic) into paraaminobenzoic acid (PABA) an inactive metabolite </li></ul>
  82. 82. Increased Therapeutic Action <ul><li>Metabolism can increase the effectiveness of some drugs. </li></ul><ul><li>This concept is illustrated by the conversion of codeine into morphine. </li></ul><ul><li>The analgesic activity of morphine is so much greater than that of codeine that formation of morphine may account for virtually all the pain relief that occurs following codeine administration </li></ul>
  83. 83. Activation of Prodrugs <ul><li>. A prodrug is a compound that is pharmacologically inactive as administered and then undergoes conversion to its active form within the body. </li></ul><ul><li>Activation of a prodrug is illustrated by the metabolic conversion of prazepam into desmethyldiazepam . </li></ul><ul><li>Prazepam is a close relative of diazepam, a drug familiar to us under the trade name Valium. </li></ul>
  84. 84. Increased or Decreased Toxicity. <ul><li>. By converting drugs into inactive forms, metabolism can decrease toxicity. Conversely, metabolism can increase the potential for harm by converting relatively safe compounds into forms that are toxic. </li></ul><ul><li>Increased toxicity is illustrated by the conversion of acetaminophen Tylenol, into a hepatotoxic metabolite. </li></ul><ul><li>It is this product of metabolism, and not acetaminophen itself, that causes injury when acetaminophen is taken in overdose </li></ul>
  85. 85. Special Considerations in Drug Metabolism <ul><li>  Age.   </li></ul><ul><li>The drug-metabolizing capacity of infants is limited. The liver does not develop its full capacity to metabolize drugs until about 1 year after birth. </li></ul><ul><li>During the time prior to hepatic maturation, infants are especially sensitive to drugs, and care must be taken to avoid injury </li></ul>
  86. 86. Special Considerations in Drug Metabolism <ul><li>Induction of Drug Metabolizing Enzymes </li></ul><ul><li>Some drugs act on the liver to increase rates of drug metabolism </li></ul><ul><li>This process of stimulating enzyme synthesis is known as induction. </li></ul>
  87. 87. Special Considerations in Drug Metabolism <ul><li>First-Pass Effect </li></ul><ul><li>The term first-pass effect refers to the rapid hepatic inactivation of certain oral drugs. </li></ul><ul><li>If the capacity of the liver to metabolize a drug is extremely high, that drug can be completely inactivated on its first pass through the liver. As a result, no therapeutic effects can occur. </li></ul>
  88. 88. Special Considerations in Drug Metabolism <ul><li>Nutritional Status. </li></ul><ul><li>Hepatic drug-metabolizing enzymes require a number of cofactors to function. </li></ul><ul><li>In the malnourished patient, these cofactors may be deficient, causing drug metabolism to be compromised. </li></ul>
  89. 89. Special Considerations in Drug Metabolism <ul><li>Competition Between Drugs </li></ul>
  90. 90. EXCRETION <ul><li>Drug excretion is defined as the removal of drugs from the body. </li></ul><ul><li>Drugs and their metabolites can exit the body in urine, bile, Sweat, saliva, breast milk, and expired air. </li></ul><ul><li>The most important organ for drug excretion is the kidney. </li></ul>
  91. 91. EXCRETION <ul><li>Renal Drug Excretion </li></ul><ul><li>The kidneys account for the majority of drug excretion. When the kidneys are healthy, they serve to limit the duration of action of many drugs. </li></ul><ul><li>Renal failure - both the duration and intensity of drug responses may increase. </li></ul><ul><li>  </li></ul>
  92. 92. Plasma Drug Levels <ul><li>Clinical Significance of Plasma Drug Levels </li></ul><ul><li>There is a direct correlation between therapeutic and toxic responses and the amount of drug present in plasma. </li></ul>
  93. 93. Plasma Concentrations <ul><li>Minimum Effective Concentration </li></ul><ul><li>The plasma drug level below which therapeutic effects will not occur </li></ul><ul><li>Toxic Concentration . </li></ul><ul><li>The plasma level at which toxic effects begin is termed the toxic concentration. Doses must be kept small enough so that the toxic concentration is not reached </li></ul>
  94. 94. Therapeutic Range <ul><li>The objective of drug dosing is to maintain plasma drug levels within the therapeutic range. </li></ul>
  95. 95. Single-Dose Time Course <ul><li>Because responses cannot occur until plasma drug levels have reached the MEC, there is a period of latency between drug administration and onset of effects. </li></ul><ul><li>The extent of this delay is determined by the rate of absorption. </li></ul>
  96. 96. <ul><li>The duration of effects is determined largely by the combination of metabolism and excretion. </li></ul><ul><li>As long as drug levels remain above the MEC, therapeutic responses will be maintained </li></ul>
  97. 97. Drug Half-Life <ul><li>The time required for the amount of drug in the body to decrease by 50% </li></ul><ul><li>The half-life of a drug determines the dosing interval ( how much time separates each dose) </li></ul>
  98. 98. Plateau Drug Levels <ul><li>Administering repeated doses will cause a drug to build up in the body until a plateau (steady level) has been achieved </li></ul><ul><li>When the amount of drug eliminated between doses equals the dose administered, average drug levels will remain constant and plateau will have been reached </li></ul>
  99. 99. Plateau Drug Levels <ul><li>When a drug is administered repeatedly in the same dose, plateau will be reached in approximately four half-lives </li></ul>
  100. 100. Loading Doses Versus Maintenance Doses <ul><li>. When plateau must be achieved more quickly, a large initial dose can be administered. This large initial dose is called a loading dose . </li></ul><ul><li>After high drug levels have been established with a loading dose, plateau can be maintained by giving smaller doses. These smaller doses are referred to as maintenance doses. </li></ul>
  101. 101. Plateau Drug Levels <ul><li>When drug administration is discontinued, most (94%) of the drug in the body will be eliminated over an interval equal to about four half-live </li></ul>
  102. 102. Pharmacodynamics <ul><li>The study of the biochemical and physiologic effects of drugs and the molecular mechanisms by which those effects are produced. </li></ul><ul><li>Pharmacodynamics is the study of what drugs do to the body and how they do it. </li></ul>
  103. 103. <ul><li>Maximal efficacy is defined as the largest effect that a drug can produce. </li></ul><ul><li>Potency is how much drug must be administered to elicit a desired response. </li></ul>
  104. 104. The Four Primary Receptor Families <ul><li>The Four Primary Receptor Families </li></ul><ul><li>Cell membrane-embedded enzymes </li></ul><ul><li>Ligand-gated ion channels </li></ul><ul><li>G protein-coupled receptor systems </li></ul><ul><li>Transcription factors. </li></ul>
  105. 106. Cell membrane-embedded enzymes <ul><li>Receptors of this type span the cell membrane. The ligand-binding domain is located on the cell surface, and the enzyme's catalytic site is inside. </li></ul><ul><li>Binding of an endogenous regulatory molecule or agonist drug (one that mimics the action of the endogenous regulatory molecule) activates the enzyme, </li></ul><ul><li>.. </li></ul>
  106. 107. Cell membrane-embedded enzymes <ul><li>. Responses to activation of these receptors occur in seconds. </li></ul><ul><li>Insulin is a good example of an endogenous ligand that acts through this type of receptor. </li></ul>
  107. 108. Ligand-Gated Ion Channels. <ul><li>Ligand-Gated Ion Channels. Like membrane-embedded enzymes, ligand-gated ion channels span the cell membrane. </li></ul><ul><li>The function of these receptors is to regulate flow of ions into and out of cell. </li></ul><ul><li>Each ligand-gated channel is specific for a particular ion (eg, Na+, CaH) </li></ul>
  108. 109. Ligand-Gated Ion Channels <ul><li>Responses to activation of a ligand-gated ion channel are extremely fast, usually occurring in milliseconds. </li></ul><ul><li>Several neurotransmitters, including acetyl­choline and gamma-aminobutyric acid (GABA), act through this type of receptor. </li></ul>
  109. 110. G Protein-Coupled Receptor Systems <ul><li>. G protein­coupled receptor systems have three components: the receptor itself, G protein (so named because it binds GTP), and an effector (typically an ion channel or an enzyme). These systems work as follows: binding of an endogenous ligand or agonist drug activates the receptor, which in turn activates G protein, which in turn activates the effector. </li></ul>
  110. 111. G Protein-Coupled Receptor Systems <ul><li>Responses to activation of this type of system develop rapidly. Numerous endogenous ligands, including NE, serotonin, histamine, and many peptide hormones, act through G protein-coupled receptor systems. </li></ul>
  111. 112. Transcription Factors <ul><li>. Transcription factors differ from other receptors in two ways: </li></ul><ul><li>(I) transcription factors are found within the cell rather than on the surrace, </li></ul><ul><li>(2) responses to activation of these receptors are delayed. </li></ul>
  112. 113. Transcription Factors <ul><li>Transcription factors are situated on DNA in the cell nucleus. </li></ul><ul><li>Their function is to regulate protein synthesis. Activation of these receptors by endogenous ligands or by agonist drugs stimulates transcription of messenger RNA molecules, which then act as templates for synthesis of specific proteins. </li></ul>
  113. 114. Transcription Factors <ul><li>Because transcription factors are intracellular, they can be activated only by ligands that are sufficiently lipid soluble to cross the cell membrane </li></ul>
  114. 115. Transcription Factors <ul><li>Endogenous ligands that act through transcription factors include thyroid hormone and all of the steroid hormones ( progesterone, testosterone, cortisol). </li></ul>
  115. 116. Agonists, Antagonists, and Partial Agonists <ul><li>Agonists are molecules that activate receptors </li></ul><ul><li>Antagonists produce their effects by preventing receptor activation by endogenous regulatory molecules and drugs </li></ul><ul><li>Partial agonist is an agonist that has only moderate intrinsic activity., </li></ul><ul><li>The maximal effect that a partial agonist can produce is lower than that of a full agonist. </li></ul>
  116. 117. Noncompetitive Versus Competitive Antagonists <ul><li>Noncompetitive (Insurmountable) Antagonists. </li></ul><ul><li>Non­competitive antagonists bind irreversibly to receptors. </li></ul><ul><li>The effect of irreversible binding is equivalent to reducing the total number of receptors available for activation by an agonist </li></ul>
  117. 118. Noncompetitive Versus Competitive Antagonists <ul><li>Competitive (Surmountable) Antagonists. Competitive antagonists bind reversibly to receptors. </li></ul><ul><li>Competitive antagonists produce receptor blockade by competing with agonists for receptor binding. If an agonist and a competitive antagonist have equal affinity for a palticular receptor, then the receptor will be occupied by whichever agent-agonist or antagonist-is present in the highest con­centration. </li></ul>
  118. 119. Regulation of Receptor Sensitivity <ul><li>Receptors are dynamic components of the cell. </li></ul><ul><li>In response to continuous activation or continuous inhibition, the number of receptors on the cell surface can change, as can their sensitivity to agonist molecules (drugs and endogenous ligands). </li></ul>
  119. 120. EDso <ul><li>EDso is an abbreviation for average effective dose. </li></ul><ul><li>The ED so is defined as the dose that is required to produce a defined therapeutic response in 50% of the population. </li></ul><ul><li>The EDso can be considered a &quot;standard&quot; dose and, as such, is frequently the dose selected for initial treatment. </li></ul>
  120. 121. The Therapeutic Index <ul><li>The therapeutic index is a measure of a drug's safety. </li></ul><ul><li>The therapeutic index, determined using laboratory animals, is defined as the ratio of a drug's LDso to its EDso. (The LDso, or average lethal dose, is the dose that is lethal to 50% of the animals treated.) </li></ul>
  121. 122. Therapeutic Index <ul><li>A large (or high) therapeutic index indicates </li></ul><ul><li>that a drug is relatively safe. </li></ul><ul><li>Conversely, a small (or low) therapeutic index indicates that a drug is relatively unsafe. </li></ul>
  124. 125. Drug Interactions <ul><li>Drug-drug interactions </li></ul><ul><li>Drug-drug interactions can occur whenever a patient takes two or more drugs. </li></ul><ul><li>Some interactions are both intended and desired, as when we combine drugs to treat hypertension </li></ul>
  125. 126. Drug Interactions <ul><li>Drug interactions occur because patients frequently take more than one drug. </li></ul><ul><li>They may take multiple drugs to treat a single disorder. </li></ul><ul><li>They may have multiple disorders that require treatment with different drugs. </li></ul><ul><li>They may take over-the­counter drugs in addition to prescription medicines. </li></ul><ul><li>And they may take caffeine, nicotine, alcohol, and other drugs that have nothing to do with illness. </li></ul>
  126. 127. Consequences of Drug-Drug Interaction <ul><li>When drug A interacts with drug B, there are three possible outcomes: </li></ul><ul><li>1) drug A may intensify the effects of drug (2) drug A may reduce the effects of drug </li></ul><ul><li>(3) the combination may produce a new response not seen with either drug alone. </li></ul>
  127. 128. Intensification of Effects <ul><li>When a patient is taking two medications, one drug may intensify the effects of the other. </li></ul><ul><li>This type of interaction is often termed potentiative. </li></ul><ul><li>Potentiative interactions may be beneficial or detrimental. </li></ul><ul><li>A potentiative interaction that enhances therapeutic effects is clearly beneficial. </li></ul><ul><li>Conversely, a potentiative interaction that intensifies adverse effects is clearly detrimental. </li></ul>
  128. 129. Increased Therapeutic Effects <ul><li>The interaction between sulbactam and ampicillin represents a beneficial potentiative interaction. </li></ul><ul><li>When administered alone, ampicillin undergoes rapid inactivation by bacterial enzymes. </li></ul><ul><li>Sulbactam inhibitsl those enzymes, and thereby prolongs and intensifies ampicillin's therapeutic effects. </li></ul>
  129. 130. Increased Adverse Effects <ul><li>. The interaction between aspirin and warfarin represents a detrimental potentiative interaction. Warfarin is an anticoagulant used to suppress formation of blood clots. Unfortunately, if the dosage of warfarin is too hight the patient is at lisk of spontaneous bleeding. </li></ul><ul><li>For therapy to be safe and effective, the dosage must be high enough to suppress clot formation but not so high that spontaneous bleeding occurs. </li></ul>
  130. 131. Reduction of Effects <ul><li>Interactions that result in reduced drug effects are often termed inhibitory. </li></ul><ul><li>As with potentiative interactions, inhibitory interactions can be beneficial or detrimental. Inhibitory inter actions that reduce toxicity are beneficial. </li></ul><ul><li>Conversely, inhibitory interactions that reduce therapeutic effects are detrimental. </li></ul>
  131. 132. Reduced Therapeutic Effects <ul><li>. The interaction between propranolol and albuterol represents a detrimental inhibitory interaction. </li></ul><ul><li>Albuterol is taken by people with asthma to dilate the bronchi. </li></ul><ul><li>Propranolol a drug for cardiovascular disorders, can act in the lung to block the effects of albuterol. </li></ul><ul><li>if propranolol and albuterol are taken together, propranolol can reduce albuterol's therapeutic effects. </li></ul><ul><li>Inhibitory actions such as this, which can result in therapeutic failure, are clearly detrimental. </li></ul><ul><li>  </li></ul>
  132. 133. Reduced Adverse Effects <ul><li>. The use of naloxone to treat morphine overdose is an excellent example of a beneficial inhibitory interaction. When administered in excessive dosage, morphine can produce coma and profound respiratory depression death can result. </li></ul><ul><li>Naloxone, a drug that blocks morphine's actions, can completely reverse all symptoms of toxicity. The benefits of such an inhibitory interaction are obvious. </li></ul>
  133. 134. Creation of a Unique Response <ul><li>Rarely, the combination of two drugs produces a new response not seen with either agent alone. </li></ul><ul><li>To illustrate, let's consider the combination of alcohol with disulfiram [Antabuse], a drug used to treat alcoholism. </li></ul><ul><li>When alcohol and disulfiram are combined, a host of unpleasant and dangerous responses can result. These effects do not occur when disulfiram or alcohol is used alone. </li></ul>
  134. 135. Basic Mechanisms of Drug-Drug Interactions <ul><li>Drugs can interact through four basic mechanisms: </li></ul><ul><li>direct chemical or physical interaction </li></ul><ul><li>pharmacokinetic interaction </li></ul><ul><li>(3) phamacodynamic interaction </li></ul><ul><li>(4) combined toxicity. </li></ul>
  135. 136. Direct Chemical or Physical Interaction <ul><li>Some drugs, because of their physical or chemical properties, can undergo direct interaction with other drugs. </li></ul><ul><li>Direct physical and chemical interactions usually render both drugs inactive. </li></ul><ul><li>Never combine two or more drugs in the same container unless it has been established that a direct interaction will not occur. </li></ul>
  136. 137. Pharmacokinetic Interactions <ul><li>Drug interactions can affect all four of the basic pharmacokinetIc processes., </li></ul><ul><li>when two drugs are taken together, one may alter the absorption, distribution, metabolism, or excretIon of the other. </li></ul>
  137. 138. Altered Distribution <ul><li>There are two principal mechanisms by which one drug can alter the distribution of another: </li></ul><ul><li>Competition for protein binding </li></ul><ul><li>Alteration of extracellular pH. </li></ul>
  138. 139. Competition for Protein Binding <ul><li>. When two drugs bind to the same site on plasma albumin, co administration of those drugs produces competition for binding. </li></ul><ul><li>As a result, binding of one or both agents is reduced, causing plasma levels of free drug to rise. </li></ul><ul><li>In theory, the increase in free drug can intensify effects. </li></ul><ul><li>However, since the newly freed drug usually undergoes rapid elimination, the increase in plasma levels of free drug is rarely sustained or significant. </li></ul>
  139. 140. Altered Metabolism <ul><li>. Altered metabolism is one of the most important-and most complex-mechanisms by which drugs interact. </li></ul><ul><li>Some drugs increase the metabolism of other drugs, and some drugs decrease the metabolism of other drugs. </li></ul>
  140. 141. Altered Renal Excretion
  141. 142. Pharmacodynamic Interactions <ul><li>Pharmacodynamic interactions are of two basic types: </li></ul><ul><li>(1) interactions in which the interacting drugs act at the same site </li></ul><ul><li>(2) interactions in which the interacting drugs act at separate sites </li></ul><ul><li>Pharmacodynamic interactions may be potentiative or inhibitory, and are of great clinIcal significance </li></ul>
  142. 143. Pharmacodynamic Interactions <ul><li>Interactions at the Same Receptor. Interactions that occur at the same receptor are almost always inhibitory. </li></ul><ul><li>Interactions Resulting from Actions at Separate Sites . </li></ul><ul><li>Interactions resulting from effects produced at different sites may be potentiative or inhibitory . </li></ul>
  143. 144. Interactions Resulting from Actions at Separate Sites <ul><li>The interaction between two diuretics-hydrochlorothiazide and spironolactone illustrates how the effects of a drug acting at one site can counteract the effects of a second drug acting at a different site. </li></ul><ul><li>Hydrochlorothiazide acts on the distal convoluted tubule of the nephron to increase excretion of potassium. </li></ul><ul><li>Acting at a different site in the kidney, spironolactone works to decrease renal excretion of potassium. </li></ul>
  144. 145. Interactions Resulting from Actions at Separate Sites . <ul><li>Consequently, when these two drugs are administered together,the potassium­sparing effects of spironolactone tend to balance the potassium-wasting effects of hydrochlorothiazide, leaving renal excretion of potassium at about the same level it would have been had no drugs been given at all. </li></ul>
  145. 146. Combined Toxicity
  146. 147. Minimizing Adverse Drug-Drug Interactions <ul><li>We can minimize adverse interactions in several ways. </li></ul><ul><li>The most obvious is to minimize the number of drugs a patient receives. </li></ul><ul><li>A second and equally important way to avoid detrimental interactions is to take a thorough drug history. </li></ul>
  147. 148. DRUG-FOOD INTERACTIONS <ul><li>Drug-food interactions are both important and poorly under­stood. </li></ul><ul><li>They are important because they can result in toxicity or therapeutic failure. </li></ul><ul><li>They are poorly understood because research has been sorely lacking. </li></ul>
  148. 149. DRUG-FOOD INTERACTIONS <ul><li>Impact of Food on Drug Absorption </li></ul><ul><li>Reducing the rate of absorption merely delays the onset of effects; peak effects are not lowered. </li></ul><ul><li>In contrast, reducing the extent of absorption reduces the intensity of peak responses. </li></ul>
  149. 150. DRUG-FOOD INTERACTIONS <ul><li>The interaction between calcium-containing foods and tetracycline antibiotics is perhaps the classic example of food reducing drug absorption. </li></ul><ul><li>Tetracyclines bind with calcium to form an insoluble and nonabsorbable complex. </li></ul><ul><li>Hence, if tetracyclines are administered with milk products or calcium supplements, absorption is reduced and antibacterial effects may be lost. </li></ul>
  150. 151. DRUG-FOOD INTERACTIONS <ul><li>High-fiber foods can reduce absorption of some drugs. </li></ul><ul><li>For example, absorption of digoxin [Lanoxin], a drug used for cardiac disorders, is reduced significantly by wheat bran, rolled oats, and sunflower seeds. </li></ul><ul><li>Since digoxin has a low therapeutic index, reduced absorption can result in therapeutic failure </li></ul>
  151. 152. Impact of Food on Drug Metabolism: The Grapefruit Juice Effect <ul><li>Grapefruit juice can inhibit the metabolism of certain drugs, </li></ul><ul><li>Thereby raising their blood levels. </li></ul><ul><li>The effect is quite remarkable. </li></ul><ul><li>In one study, coadministration of grapefruit juice produced a 406% increase in blood levels of felodipin </li></ul>
  152. 153. Impact of Food on Drug Toxicity <ul><li>Drug-food interactions sometimes increase toxicity. </li></ul><ul><li>The most dramatic example is the interaction between monoamine oxidase (MAO) inhibitors (a family of antidepressants) and foods rich in tyramine (eg, aged cheeses, yeast extracts, Chianti wine). </li></ul><ul><li>If an MAO inhibitor is combined with these foods, blood pressure can rise to a life-threatening level. </li></ul>
  153. 154. Impact of Food on Drug Action <ul><li>Although most drug-food interactions concern drug absorption or drug metabolism, food may also (rarely) have a direct impact on drug action. </li></ul><ul><li>For example, foods rich in vitamin K broccoli, Brussels sprouts, cabbage) can reduce the effects of warfarin, an anticoagulant. </li></ul>
  154. 155. Timing of Drug Administration with Respect to Meals
  156. 157. ADVERSE DRUG REACTIONS <ul><li>An adverse drug reaction (ADR), as defined by the World Health Organization, is any noxious, unintended, and undesired effect that occurs at normal drug doses . </li></ul><ul><li>Fortunately, when drugs are used properly , many ADRs can be avoided, or at least kept to a minimum </li></ul>
  157. 158. ADVERSE DRUG REACTIONS <ul><li>Drugs can adversely affect all body systems in varying degrees of intensity. </li></ul><ul><li>Among the more mild reactions are drowsiness, nausea, itching, and rash. </li></ul><ul><li>Severe reactions include respiratory depression, neutropenia, hepatocellular injury, anaphylaxis, and hemorrhage </li></ul><ul><li>all of which can result in death . </li></ul>
  158. 159. ADVERSE DRUG REACTIONS <ul><li>Although ADRs can occur in all patients, some patients are more vulnerable than others. </li></ul><ul><li>Adverse events are most common in the elderly and the very young. (Patients over 60 account for nearly 50% of all ADR cases.) </li></ul><ul><li>Severe illness also increases the risk of an ADR. Likewise, adverse events are more common in patients receiving multiple drugs than in patients taking just one. </li></ul><ul><li>  </li></ul>
  159. 160. ADVERSE DRUG REACTIONS <ul><li>Side Effect </li></ul><ul><li>A side effect is formally defined as a nearly unavoidable secondary drug effect produced at therapeutic doses. </li></ul><ul><li>Common examples include drowsiness caused by traditional antihistamines and gastric initation caused by aspirin. </li></ul><ul><li>Side effects are generally predictable and their intensity is dose dependent </li></ul>
  160. 161. ADVERSE DRUG REACTIONS <ul><li>Toxicity </li></ul><ul><li>The formal definition of toxicity is an adverse drug reaction caused by excessive dosing. </li></ul><ul><li>Examples include coma from an overdose of morphine and severe hypoglycemia from an overdose of insulin term </li></ul><ul><li>Toxicity has come to mean any severe ADR regardless of the dose that caused it. </li></ul>
  161. 162. ADVERSE DRUG REACTIONS <ul><li>Allergic Reaction </li></ul><ul><li>An allergic reaction is an immune response. </li></ul><ul><li>For an allergic reaction to occur, there must be prior sensitization of the immune system. </li></ul><ul><li>Once the immune system has been sensitized to a drug, re-exposure to that drug can trigger an allergic response. </li></ul><ul><li>The intensity of allergic reactions can range from mild itching to severe rash to anaphylaxis. ( </li></ul>
  162. 163. ADVERSE DRUG REACTIONS <ul><li>Anaphylaxis is a life-threatening response characterized by bronchospasm, laryngeal edema, and a precipitous drop in blood pressure. </li></ul><ul><li>Estimates suggest that less than 10% of ADRs are of the allergic type. </li></ul>
  163. 164. ADVERSE DRUG REACTIONS <ul><li>The intensity of an allergic reaction is determined primarily by the degree of sensitization of the immune system -not by drug dosage </li></ul><ul><li>T he intensity of allergic reactions is largely independent of dosage </li></ul><ul><li>Very few medications cause severe allergic reactions. In fact, most serious reactions are caused by just one drug family-the penicillins </li></ul>
  164. 165. ADVERSE DRUG REACTIONS <ul><li>Idiosyncratic Effect </li></ul><ul><li>An idiosyncratic effect is defined as an uncommon drug response resulting from a genetic predisposition succinylcholine, a drug used to produce flaccid paralysis of skeletal muscle. </li></ul><ul><li>In most patients, succinylcholine-induced paralysis is brief, lasting only a few minutes. In contrast, genetically predisposed patients may become paralyzed for hours </li></ul>
  165. 166. ADVERSE DRUG REACTIONS <ul><li>Iatrogenic Disease </li></ul><ul><li>An iatrogenic disease is a disease produced by a physician. </li></ul><ul><li>The term iatrogenic disease is also used to denote a disease produced by drugs. </li></ul>
  166. 167. ADVERSE DRUG REACTIONS Physical Dependence <ul><li>Physical dependence develops during long-term use of certain drugs, such as opioids, alcohol, barbiturates, and amphetamines. </li></ul><ul><li>Physical dependence is a state in which the body has adapted to prolonged drug exposure in such a way that an abstinence syndrome will result if drug use is discontinued </li></ul>
  167. 168. ADVERSE DRUG REACTIONS Physical Dependence <ul><li>The precise nature of the abstinence syndrome is determined by the drug involved. </li></ul><ul><li>Patients should be warned against abrupt discontinuation of any medication without first consulting a knowledgeable health professional. </li></ul>
  168. 169. ADVERSE DRUG REACTIONS <ul><li>Carcinogenic Effect </li></ul><ul><li>R efers to the ability of certain medications and environmental chemicals to cause cancers. </li></ul>
  169. 170. ADVERSE DRUG REACTIONS <ul><li>Teratogenic Effect </li></ul><ul><li>A teratogenic effect can be defined as a drug-induced birth defect. </li></ul><ul><li>Medicines and other chemicals capable of causing birth defects are called teratogen </li></ul>
  170. 171. Organ-Specific Toxicity
  171. 172. Hepatotoxic Drugs <ul><li>Drugs are the leading cause of acute liver failure. </li></ul><ul><li>Most cases end with a liver transplant or in death. </li></ul><ul><li>The ability to cause severe liver damage is the most common reason for withdrawing an approved drug from the market. </li></ul>
  172. 173. Altered Cardiac Function
  173. 174. Identifying Adverse Drug Reactions <ul><li>Did symptoms appear shortly after the drug was first used? </li></ul><ul><li>Did symptoms abate when the drug was discontinued? </li></ul><ul><li>Did symptoms reappear when the drug was reinstituted? . </li></ul><ul><li>Is the illness itself sufficient to explain the event? </li></ul><ul><li>Are other drugs in the regimen sufficient to explain the event? </li></ul>
  174. 175. Ways to Minimize Adverse Drug Reactions <ul><li>The nurse must evaluate patients for ADRs and educate patients in ways to avoid or minimize harm </li></ul><ul><li>Anticipation of ADRs can help minimize them. </li></ul><ul><li>Both the nurse and the patient should know the major ADRs that a drug can produce. </li></ul>
  175. 176. Monitoring organ Toxicity <ul><li>For drugs that are toxic to the liver, the patient should be monitored for signs and symptoms of liver damage ( jaundice, dark urine, light-colored stools, nausea, vomiting, malaise, abdominal discomfort, loss of appetite), and periodic LFTs should be performed </li></ul>
  176. 177. Monitoring organ Toxicity <ul><li>For drugs that are toxic to the kidneys, the patient should undergo routine urinalysis and measurement of serum creatinine . </li></ul><ul><li>For drugs that are toxic to bone marrow, periodic blood cell counts are required. </li></ul><ul><li>  </li></ul>
  177. 178. MEDICATION ERRORS <ul><li>Medication errors are a major cause of morbidity and mortality </li></ul><ul><li>a medication error as &quot;any preventable event that may cause or lead to inappropriate medication use or patient harm, while the medication is in the control of the healthcare professional, patient, or consumer. </li></ul>
  178. 179. MEDICATION ERRORS <ul><li>Because the nurse is the last person who can catch mistakes made by others, and because no one is there to catch mistakes the nurse might make, the nurse bears a heavy responsibility for ensuring patient safety. </li></ul><ul><li>Can you think of a better reason to learn all you can about drugs? </li></ul>
  179. 180. Types of Medication Errors
  180. 181. Causes of Medication Errors
  181. 182. Individual Variation in Drug Responses
  182. 183. WEIGHT AND COMPOSITION <ul><li>Dosages must be adapted to the size of the patient. When adjusting dosage to account for body weight, the clinician may base the adjustment on body surface area rather than on weight .Because surface area determinations account not only for the patient's weight but also for how fat or lean he or she may be. </li></ul>
  183. 184. AGE <ul><li>Drug sensitivity varies with age. </li></ul><ul><li>In the very young, heightened drug sensitivity is the result of organ immaturity </li></ul><ul><li>In the elderly, heightened sensitivity results largely from organ degeneration </li></ul>
  184. 185. PATHOPHYSIOLOGY <ul><li>Abnormal physiology can alter responses to drugs </li></ul>
  185. 186. Kidney disease <ul><li>Can reduce drug excretion, causing drugs to accumulate in the body. </li></ul><ul><li>If dosage is not lowered, drugs may accumulate to toxic levels. </li></ul><ul><li>Accordingly, if a patient is taking a drug that is eliminated by the kidneys, and if renal failure develops, dosage must be decreased. </li></ul>
  186. 187. Liver Disease <ul><li>Like kidney disease, liver disease can cause drugs to accumulate. Recall that the liver is the major site of drug metabolism. </li></ul><ul><li>Hence, if the liver ceases to function, rates of metabolism will fall and drug levels will climb. </li></ul><ul><li>To prevent accumulation to toxic levels, patients with liver disease should have their dosages reduced. </li></ul>
  187. 188. Acid-Base Imbalance <ul><li>By altering pH partitioning, changes in acid-base status can alter the absorption, distribution, metabolism, and excretion of drugs. </li></ul>
  188. 189. Altered Electrolyte Status <ul><li>Electrolytes ( potassium, sodium, calcium, magnesium) have important roles in cell physiology. </li></ul><ul><li>Consequently, when electrolyte levels become disturbed, multiple cellular processes can be disrupted. </li></ul><ul><li>Most important example of an altered drug effect occurring in response to electrolyte imbalance involves D igoxin </li></ul>
  189. 190. TOLERANCE <ul><li>Tolerance can be defined as decreased responsiveness to a drug as a result of repeated drug administration. </li></ul><ul><li>Patients who are tolerant to a drug require higher doses to produce effects equivalent to those that could be achieved with lower doses </li></ul><ul><li>There are three categories of drug tolerance: Pharmacodynamic tolerance </li></ul><ul><li>Metabolic tolerance </li></ul><ul><li>Tachyphylaxis. </li></ul>
  190. 191. Pharmacodynamic Tolerance <ul><li>Pharmacodynamic tolerance refers to the familiar type of tolerance associated with long-term administration of drugs such as morphine and heroin </li></ul><ul><li>Pharmacodynamic tolerance is thought to result from adaptive processes that occur in response to chronic receptor occupation. </li></ul>
  191. 192. Metabolic Tolerance <ul><li>Metabolic tolerance is defined as tolerance resulting from accelerated drug metabolism </li></ul><ul><li>. This form of tolerance is brought about by the ability of certain drugs to induce synthesis of hepatic drug-metabolizing enzymes </li></ul><ul><li>Because of increased metabolism, dosage must be increased to maintain therapeutic drug levels </li></ul>
  192. 193. Tachyphylaxis <ul><li>Tachyphylaxis is a form of tolerance that can be defined as a reductic drug responsiveness brought on by repeated dosing over a short time. </li></ul><ul><li>U nlike pharmacodynamic and metabolic tolerance, which take days to develop tachyphylaxis occurs quickly. </li></ul><ul><li>Transdermal nitroglycerin provides a good example </li></ul>
  193. 194. Placebo Effect <ul><li>In pharmacology, the placebo effect is defined as that component of a drug response that is caused by </li></ul><ul><li>Psychologic factors and not by the biochemical or physiologic properties of the drug. </li></ul><ul><li>Although it is impossible to assess with precision contribution that psychologic factors make to the overall response to any particular drug </li></ul>
  194. 195. VARIABILITY IN ABSORPTION <ul><li>Both the rate and extent of drug absorption can vary among patients </li></ul>
  195. 196. Bioavailability <ul><li>Refers to the ability of a drug to reach the systemic circulation from its site of administration. . </li></ul><ul><li>Different preparations of the same drug can vary in bioavailability </li></ul><ul><li>Such factors as tablet disintegration time, enteric coatings, and sustained-release formulations can alter bioavailability </li></ul>
  196. 197. Bioavailability <ul><li>Differences in bioavailability are of greatest concern for drugs with a narrow therapeutic range. </li></ul>
  197. 198. GENETIC <ul><li>A patient's unique genetic makeup can lead to drug responses that are qualitatively and quantitatively different from those of the population at large </li></ul><ul><li>The major underlying causes of altered responses are alterations in genes that code for drug metabolizing enzymes and drug targets </li></ul>
  198. 199. GENDER <ul><li>Men and women can respond differently to the same drug </li></ul><ul><li>Alcohol is metabolized more slowly by women than by men. </li></ul><ul><li>As a result, a woman who drinks the same amount as a man (on a weight-adjusted basis) will become more intoxicated . </li></ul>
  199. 200. GENDER <ul><li>Certain opioid analgesics are much more effective in women than in men. </li></ul><ul><li>As a result, pain relief can be achieved at lower doses in women </li></ul>
  200. 201. RACE <ul><li>Race-related drug responses have two primary determinants: </li></ul><ul><li>genetic variations and psychosocial factors </li></ul>
  202. 203. DIET <ul><li>Starvation can reduce protein binding of drugs by decreasing the level of plasma albumin </li></ul><ul><li>Because of reduced binding, levels of free drug rise, thereby making drug responses more intense. </li></ul>